Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock

Daniel E. Leisman; Damian R. Handisides; Lakhmir S. Chawla; Timothy E. Albertson; Laurence W. Busse; David W. Boldt; Adam M. Deane; Michelle N. Gong; Kealy R. Ham; Ashish K. Khanna; Marlies Ostermann; Michael T. McCurdy; B. Taylor Thompson; James S. Tumlin; Christopher D. Adams; Tony N. Hodges; Rinaldo Bellomo

doi:10.1186/s13613-023-01227-5

Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock

Daniel E. Leisman, Damian R. Handisides, Lakhmir S. Chawla, Timothy E. Albertson, Laurence W. Busse, David W. Boldt, Adam M. Deane, Michelle N. Gong, Kealy R. Ham, Ashish K. Khanna, Marlies Ostermann, Michael T. McCurdy, B. Taylor Thompson, James S. Tumlin, Christopher D. Adams, Tony N. Hodges, Rinaldo Bellomo

Medicine

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Abstract

Background: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO₂/FiO₂-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. Results: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH₂O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH₂O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH₂O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. Conclusions: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Original language	English (US)
Article number	128
Journal	Annals of Intensive Care
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s13613-023-01227-5
State	Published - Dec 2023

Keywords

ARDS
Angiotensin II
Norepinephrine
Renin–angiotensin system
Septic
Shock

ASJC Scopus subject areas

Critical Care and Intensive Care Medicine

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10.1186/s13613-023-01227-5

Cite this

Leisman, D. E., Handisides, D. R., Chawla, L. S., Albertson, T. E., Busse, L. W., Boldt, D. W., Deane, A. M., Gong, M. N., Ham, K. R., Khanna, A. K., Ostermann, M., McCurdy, M. T., Thompson, B. T., Tumlin, J. S., Adams, C. D., Hodges, T. N., & Bellomo, R. (2023). Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock. Annals of Intensive Care, 13(1), Article 128. https://doi.org/10.1186/s13613-023-01227-5

Leisman, DE, Handisides, DR, Chawla, LS, Albertson, TE, Busse, LW, Boldt, DW, Deane, AM, Gong, MN, Ham, KR, Khanna, AK, Ostermann, M, McCurdy, MT, Thompson, BT, Tumlin, JS, Adams, CD, Hodges, TN & Bellomo, R 2023, 'Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock', Annals of Intensive Care, vol. 13, no. 1, 128. https://doi.org/10.1186/s13613-023-01227-5

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title = "Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock",

abstract = "Background: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. Results: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. Conclusions: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).",

keywords = "ARDS, Angiotensin II, Norepinephrine, Renin–angiotensin system, Septic, Shock",

author = "Leisman, {Daniel E.} and Handisides, {Damian R.} and Chawla, {Lakhmir S.} and Albertson, {Timothy E.} and Busse, {Laurence W.} and Boldt, {David W.} and Deane, {Adam M.} and Gong, {Michelle N.} and Ham, {Kealy R.} and Khanna, {Ashish K.} and Marlies Ostermann and McCurdy, {Michael T.} and Thompson, {B. Taylor} and Tumlin, {James S.} and Adams, {Christopher D.} and Hodges, {Tony N.} and Rinaldo Bellomo",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1186/s13613-023-01227-5",

language = "English (US)",

volume = "13",

journal = "Annals of Intensive Care",

issn = "2110-5820",

publisher = "Springer-Verlag GmbH and Co. KG",

number = "1",

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TY - JOUR

T1 - Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock

AU - Leisman, Daniel E.

AU - Handisides, Damian R.

AU - Chawla, Lakhmir S.

AU - Albertson, Timothy E.

AU - Busse, Laurence W.

AU - Boldt, David W.

AU - Deane, Adam M.

AU - Gong, Michelle N.

AU - Ham, Kealy R.

AU - Khanna, Ashish K.

AU - Ostermann, Marlies

AU - McCurdy, Michael T.

AU - Thompson, B. Taylor

AU - Tumlin, James S.

AU - Adams, Christopher D.

AU - Hodges, Tony N.

AU - Bellomo, Rinaldo

PY - 2023/12

Y1 - 2023/12

N2 - Background: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. Results: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. Conclusions: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

AB - Background: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. Results: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. Conclusions: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

KW - ARDS

KW - Angiotensin II

KW - Norepinephrine

KW - Renin–angiotensin system

KW - Septic

KW - Shock

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U2 - 10.1186/s13613-023-01227-5

DO - 10.1186/s13613-023-01227-5

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SN - 2110-5820

VL - 13

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ER -

Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock

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